Acute Radiation Syndrome (ARS) (sometimes known as radiation toxicity or radiation sickness) is an acute illness caused by irradiation of a large portion of the body by a high dose of penetrating radiation; such as high energy X-rays, gamma rays, and neutrons; in a very short period of time, for example, within a matter of minutes. The major cause of this syndrome is depletion of immature parenchymal stem cells in specific tissues. Examples of people who suffered from ARS are the survivors of the Hiroshima and Nagasaki atomic bombs, the firefighters that first responded after the Chernobyl Nuclear Power Plant event in 1986, and some unintentional exposures to sterilization irradiators. In general, the radiation dose for the induction of ARS is large (i.e., greater than 0.7 Gray (Gy) or 70 rads), although mild symptoms may be observed with doses as low as 0.3 Gy or 30 rads.
Radiation gastrointestinal (GI) syndrome will usually occur with a dose greater than approximately 10 Gy (1000 rads) although some symptoms may occur as low as 6 Gy or 600 rads. Survival is extremely unlikely with this syndrome due to the destructive and irreparable changes in the GI tract and bone marrow. Radiation GI Syndrome typically can be divided into three stages. The prodromal stage manifests within several hours after exposure and symptoms include anorexia, severe nausea, vomiting, cramps, and diarrhea. The latent stage begins after about two days and the patient may appear and feel well, however, cells lining the GI tract, as well as stem cells in the bone marrow, are dying. Less than one week after exposure, the manifest illness stage begins, with symptoms including malaise, anorexia, severe diarrhea, fever, dehydration, and electrolyte imbalance. Death usually occurs within 2 weeks as a result of infection, dehydration, and electrolyte imbalance.
In addition to the treatment of acute radiation syndrome, bone marrow transplantation is currently used to treat a number of malignant and non-malignant diseases including acute and chronic leukemias, myelomas, solid tumors. However, bone marrow transplantation frequently evokes a variety of immune responses in the host, which results in rejection of the graft or graft-versus-host disease (hereinafter, referred to as “GvHD”). The conditioning regimen required prior to transplantation, designed to ablate or suppress the patient's immune system, renders the patient susceptible to neoplastic relapse or infection. Recent use of unrelated and HLA non-identical donors has unfortunately increased the incidence of GvHD. While removal of T cells from the donor marrow graft ameliorates GvHD, this strategy increases graft failure rates and markedly diminishes the therapeutically-beneficial graft-versus-tumor effect. As such, overall survival does not improve. Further, despite strong pre-clinical data, attempts to improve GvHD outcomes by diminishing inflammatory cytokine action by adding TNF antagonists to corticosteroids, the standard of care for acute GvHD, has provided limited therapeutic benefit.
Thus, there is an urgent need for alternative strategies to reduce the incidence and severity of Radiation GI Syndrome and GvHD.